There are numerous chronic diseases that are a function of altered hormonal status, especially the sex hormones. The most dominant of all of the female hormones are the estrogens which control the reproductive system as well as the function of many other cells and tissues, including bones, as well as the cardiovascular and immune systems, angiogenesis, brain and nerves, and lipid metabolism, etc.
Phytoestrogens and their metabolites (equol, etc.) possess weak estrogenic activity and compete for estrogen receptors in target tissues, including the central nervous system (hypothalamus/pituitary), uterus, breast cells, osteoblasts/osteoclasts, etc. Despite this weak intrinsic estrogenicity, the phytoestrogens may actually exert an attenuating antiestrogenic effect. See Rose, D. P., Nutrition, 8:47 to 51 (1992).
The basic factors controlling female ovarian functions are the anterior pituitary gonadotropins: follicle-stimulating hormone (FSH), which directs follicle and ovum development, and lutenizing hormone (LH) that induces estrogen secretion. The hypothalamus controls the pituitary function by means of secreting pulsatile gonadotropin releasing hormone (GnRH) production. There is a strong negative feedback inhibition of hypothalamus/pituitary function that is conducted by estrogen and inhibin (the latter is a glycoprotein that selectively inhibits FSH secretion). See Belchetz, P. E., Practitioner, 234:491 to 493 (1990).
In puberty the hypothalamic GnRH secretion is raised and this induces estrogen production through pituitary LH. Menarche, the first menstrual period, is delayed for about one to one and one half years, and the early menstrual cycles are usually not accompanied by ovulation, which may be delayed for one to one and one half years. During this overall time of 2 to 3 years there is no established feedback mechanism, either positive or negative. As a result hormonal imbalances are induced and a number of physical and psychological disorders manifest themselves.
Premenstrual tension is exhibited by a series of symptoms which occur during the second, luteal phase of the menstrual cycle. Premenstrual tension is induced by a surge of estrogen that arises because the negative feedback inhibition is altered.
Premenstrual syndrome (PMS) or premenstrual tension is a disorder that affects menstruating women one to two weeks before menses begins. The pathophysiologic mechanisms of PMS are weakly understood. One of the causes is a hormonal imbalance, an excessive estrogen level and an inadequate progesterone level. Estrogen levels in the blood and hypothalamus increase at the end of the first part of the menstrual cycle (the follicular phase); the second peak comes a week before a menstrual flow (the luteal phase). It is the second estrogen peak, which coincides with the progesterone peak, that determines the extent of the PMS.
Beside the elevated level of estrogen circulating in the blood, some PMS manifestations, such as mood or behavior, are induced by a drop in the level of biogenic amines in the central nervous system. Lower brain neurotransmitters, such as serotonin and dopamine, have been implicated in the etiology of PMS. See Taylor, D. L. et al, Neuropsychobiology, 12:16 (1984) and Kuchel, O. et al, Contrib. Nephrol., 13:27 (1978). For example it was found that 40% of depressed patients with a lower level of 5-hydroxyindoleacetic acid, the breakdown product of serotonin, had attempted suicide. See Asberg, M. New York Academy of Sciences, 1:1 (1986). Vitamin B6 is thought to be unique in its ability to normalize the metabolism of biogenic amines by increasing the activity of various pyridoxal phosphate dependent enzymatic reactions. See Berman, M. K. et al, J. Amer. Diet. Assoc., 90:859 to 861 (1990).
Another basis for implicating lower brain neurotransmitters, such as dopamine, in the etiology of PMS is chronic magnesium deficiency. See Abraham, G. E. et al, Am. J. Clin. Nutr. 34:2364. Calcium and dairy products interfere with magnesium absorption, and refined sugar increases the urinary excretion of magnesium. It was found that patients with severe PMS symptoms, such as premenstrual anxiety, irritability and nervous tension consumed five-fold more dairy products, and three-fold more refined sugar than those affected patients without these specific symptoms. See Chuong, C. J. et al, Clin. Obst. Gynecol., 35:679 to 692 (1992). Aggressive behavior in girls consuming excess dairy products, including calcium, has also been observed. On the other hand, estrogen can enhance magnesium utilization, but an estrogen-induced shift of magnesium can be deleterious when the estrogen level is high and magnesium intake is less than optimal. See Seeling, M. S., J. Am. Coll. Nutr., 12:442 to 458 (1993).
The clinical diagnosis of PMS involves a combination of physical and behavioral symptoms including headache, breast tenderness, swelling of extremities, tension, anxiety and mood swings. It is possible to differentiate women with three premenstrual symptom severity patterns: premenstrual syndrome (PMS) proper, premenstrual magnification (PMM), and low symptom (LS). See Mitchell, E. S., Nursing Res., 43:25 to 30 (1994). The incidence of premenstrual tension in gynecologic practice is estimated at 50%, but studies say that only about 2% of women actually suffer from PMS and require extensive medical treatment. See Hargrove, J. T. et al, J. Reprod. Med., 27:721 to 724 (1982). The other patients could be supported merely by diet and dietary supplements.
An ideal therapy for PMS has not been realized. The nutritional factors in pathophysiology and treatment of PMS are widely discussed, but there is no general agreement on the nutritional program best suited to treat PMS. Most American physicians recommend dietary changes in additional to nutritional supplements in management of such patients. See Lyon, K. E. et al, J. Reprod. Med., 29:705 to 711 (1984).
The limited consumption of refined sugar, salt, red meat, animal fat, alcohol, coffee, tea, chocolate, and dairy products combined with increased intake of fish, poultry, whole grains, legumes, complex carbohydrates, green leafy vegetables, cereals, and cis-linoleic acid-containing foods is a diet generally recommended to PMS sufferers. See Chuong, C. J. et al, Clin. Obst. Gynec., 35:679 to 692 (1992).
Several of these approaches to controlling PMS promote a decrease in endogenous estrogen production, and its inactivation and excretion. Indeed, the restriction of animal fat decreases cholesterol intake, and the latter is a common precursor of steroid hormones: androgens and estrogens. Leguminous seeds containing phytoestrols and saponins are potential hypocholesterolemic agents. See Ikeda I. et al, Biochem. Biophys. Acta.732:651 to 658 (1983). Whole grains, cereals, green vegetables (indole-3-carbinol), and complex carbohydrates could be effective for the conversion of estrogens into inactive metabolites. Dietary fiber significantly moves the estrogen balance into inactive forms by means of alteration of intestinal metabolism, and reduction of steroid reabsorption. See Adlercreutz, H. et al, J. Steroid Biochem., 24:289 to 296 (1986).
The beneficial effects on PMS have been shown for Vitamins A, B6 and E as well as for the minerals zinc and magnesium in several studies. See Chuong, C. J. et al, Clin. Obst. Gynec., 35:679 to 692 (1992). Multiple vitamin and mineral supplements, including their megadoses, recently have been used for the treatment of PMS. The nutritional supplement Optivite.RTM. (Optimox Corp., Torrance, Calif.) was especially formulated to provide proper nutrition for women with PMS.
Unfortunately the known effects of dietary management of PMS, including vitamin and mineral supplements, have not been clearly established, and so up to now diet management can serve only as an auxiliary treatment. There are no data about using soyfood or soy isoflavones for treatment of PMS. It was shown in a human study that consumption of 60 g of soy protein per day (containing about 60 to 80 mg of isoflavones) leads to significant changes in the menstrual cycle, with prolongation of cycle length, especially the first, follicular phase. These physiological effects are beneficial with regard to risk factors for breast and ovarian cancer, and do not prevent a pregnancy. See Setcheil, K., Role of Soy in Prevention and Treating Chronic Disease, The First Int. Symp., Mesa, Ariz. (1994). Native Chinese and Japanese women have a delayed menarche, and this effect can be explained by dietary factors, especially by the high consumption of soy food. See Yuam, J. M. et al, Cancer Res., 48:1949 (1988).
Following menopause, women become deficient in estrogen production and the negative feedback inhibition is slackened. As a direct result the activity of the hypothalamus/pituitary is enhanced. The hypothalamus is strained and influences vasomotor and thermoregulatory centers and induces hot flashes, sweats, and other symptoms of discomfort relative to climate.
Menopause is the transition from the reproductive to the non-reproductive stage of a woman's life, and it is characterized by cessation of menstruation. However, menopause has come to signify much more than simply the loss of reproductive capability, and has been associated with a number of acute and chronic conditions.
In the perimenopausal period, a complex of climacteric symptoms appears, but menstruating still continues. The early postmenopausal period is characterized by gradual cessation of climacteric symptoms. These symptoms may persist for five years or longer in 25% of the female population and may even be lifelong in a small minority.
The consequences of menopause are highly controversial and pose an important public health issue. The vasomotor climacteric symptoms (EG). (e.g. hot flashes, sweats, headaches) may be caused by an estrogen deficiency, and supplemented by a large variety of "atypical" physical and mental complaints (e.g. feeling ill at ease, tiredness, depression, sexual problems). Unfortunately for some women, the frequency of flashes is so high that life itself can be dominated by them.
The pathogenesis of menopausal symptoms is not well known. Estrogen deficiency causes two types of symptoms: those attributable to vasomotor disturbances (and secondary effects such as insomnia) and those attributable to genital atrophy. Vasomotor symptoms affect 75% of postmenopausal women, but only about 30% seek medical help for those symptoms. See Belchetz, P. E., New Engl. J. Med., 330:1062 to 1071 (1994). The alteration of negative feedback inhibition plays a key role in menopausal disorders (see above). Hormone replacement therapy (HRP) can improve the negative feedback mechanism, and decrease the level of plasma gonadotropins. See Balfour, J. A. et al, Drug, 40:561 to 582 (1990).
The beneficial effect of HRT on postmenopausal women is substantial. HRT relieves symptoms that are incontrovertibly caused by estrogen deficiency, but the response of other symptoms is less predictable. See Barlow, D. H., Brit. Med. Bull., 48:356 to 367 (1992). Many peri- and postmenopausal women have been treated with ovarian hormones in an attempt to alleviate the symptoms of menopause, and more recently in the hope of preventing osteoporosis and reducing the risk of ischemic heart disease. However, the unopposed estrogens increase the risk of endometrial and breast cancer. See Rosenberg, L. A., Am. J. Public Health, 83:1670 to 1673 (1993).
It is known that HRT by estrogens is effective to relieve the symptoms of menopause. See Brit. Med. Bull., 1992, 48:356, there is reason to expect that soybean phytoestrogens might exert a similar effect. See Dr. H. Aldercreutz et al, Lancet, 1992, 339:1233. "High Levels of Isoflavonoid Phytoestrogens may partially explain why hot flashes and other menopausal symptoms are so infrequent in Japanese women."
The non-drug treatment of menopausal symptoms includes dietary recommendations (avoid dairy and animal products), caffeine, etc.), and several nutritional supplements. These supplements include:
Vitamins: Very important vitamins include E, B5 and B6 using soy lecithin as an emulsifier for Vitamin E. Vitamin C is also helpful.
Minerals: Calcium and magnesium are important. Potassium and selenium are helpful.
Herbs Black cohosh, damiana, licorice, raspberry, sage, ginseng, dong quai, primrose oil, and blackcurrant oil.
Most of these plant products and some vitamins and minerals are used in different special menopausal formulas, which are manufactured by several producers and are available in health food stores. None of these products has proved satisfactory in the treatment of post-menopausal disorders. All of these known products merely treat symptoms and do not alleviate a hormonal deficiency. For example, it was shown that Dong quai, the dried root of Angelica sinensis in recommended doses (200 mg Rejuvex, Ginsana.RTM.) is not effective; its therapeutic dose according to Chinese medicine is 8 to 15 g per day. See Tyler, V. E., JAMA, 271:1210 (1994).